The contributions of anatomy and membrane biophysics to the function of neurons and neural circuits are best understood with the aid of computer simulations. NEURON, a program that we have developed and provide freely for MacOS, MSWindows, and UNIX, has simplified the creation and analysis of neural models for nonspecialists in numerical methods and programming. It can simulate individual neurons and networks of neurons whose properties include, but are not limited to, complex branching morphology, multiple channel types, inhomogeneous channel distribution, ionic diffusion, extracellular fields, electronic instrumentation, and artificial spiking neurons. NEURON is used by neuroscientists around the world to examine cellular and network mechanisms that are affected by diseases such as epilepsy, multiple sclerosis, and disorders of learning and memory. To continue to satisfy the evolving requirements of neuroscience research, NEURON must continue to develop in several critical areas. The existing NEURON+Java interface needs to be used for rapid development of highly diverse, domain-specific GUI tools. Application of workstation cluster resources to optimization problems needs to be as simple as a button press. The global and local variable time step methods have tremendously expanded the class of feasible simulations, often with greatly increased speed. Analysis tools must be augmented so that people can use those methods without programming. Maximizing the beneficial impact of these enhancements on neuroscience research requires dissemination of NEURON and the models that are constructed with it. Translation from physical system to conceptual model to simulation instance often requires collaboration between experimental and computational neuroscientists. To this end, we will provide user support through activities such as personal collaborations, short courses, writing articles, and creating new documentation and tutorials in traditional and digital formats. Users also need help in organizing models for effective use by others, which is indispensable for communication and reproducibility of results. This aspect of the project will employ database infrastructures developed through other initiatives such as the Human Brain Project.